Background: Lynch syndrome (LS) has been established as a significant risk factor for developing upper tract urothelial carcinoma (UTUC); however, clinicopathological characteristics and survival outcomes in this population remain contentious. This meta-analysis was designed to systematically evaluate clinicopathological features and survival outcomes in UTUC patients with microsatellite instability (MSI) or mismatch repair deficiency (dMMR), phenotypes associated with LS. Methods: A systematic literature search was conducted in PubMed, Web of Science, Embase, and Cochrane databases from January 2002 to April 2025. Clinicopathological endpoints included family history of malignancy, personal history of prior malignancies, tumor stage, tumor grade, and lymph node metastasis (LNM). The primary survival outcome was overall survival (OS). The protocol has been registered with PROSPERO. Results: Meta-analysis of 27 studies (3,545 patients) revealed that LS-UTUC was significantly associated with: a) a history of prior malignancies (OR 6.05, 95% CI 2.93; 12.48), b) lower tumor stage (OR 0.59, 95% CI 0.44; 0.79), c) predominance of G2 (G1 vs G2: OR 0.31, 95% CI 0.13; 0.72; G2 vs G3: OR 1.68, 95% CI 1.06; 2.67), and d) reduced incidence of LNM (OR 0.33, 95% CI 0.14; 0.78). Furthermore, LS-UTUC patients demonstrated notably improved OS (HR 0.63, 95% CI 0.43; 0.91). However, significant heterogeneity in diagnostic methodologies was noted, and data on other survival outcomes were too limited for analysis. Conclusions: The unique profile of LS-UTUC – encompassing high prior cancer risk, early-stage/G2-predominant pathology, and favorable survival – calls for the need for enhanced awareness of LS-UTUC among urologic oncologists. Prospective studies are warranted to standardize diagnostics and evaluate the efficacy of targeted therapies, such as immune checkpoint inhibitors, in this unique population.
Liu et al. (Tue,) studied this question.